Overview of the Proposed Resource ? Abstract The goal of the Center for Mesoscale Mapping is to drive the convergence of microscopic- and macroscopic- scale evaluation of brain structure and function for human translational neuroscience, by developing and applying tools to study the spatial distribution and temporal orchestration of mesoscopic events in the human brain. Our Collaborators will, through a dynamic ?push-pull? relationship, provide unique problems which drive the development of these tools, and in return guide us in the design and optimization of our toolbox for practical use in a variety of normal and disease settings. While there is still no formal consensus on the definition of mesoscopic within the neuroscience community, we take as our guide the spatial and temporal scales at which local groups of neurons act in coherent fashion ? in the cortex, this includes the spatial scale of columns and laminar structures (between ~0.1-1 mm), while in deeper structures includes the myriad of deep brain and brainstem nuclei. Preliminary data from our own center, and of course others throughout the world, now support the notion that we are on the threshold of being able to map, measure and perturb the human brain at these scales, and do so comprehensively across wide swaths of the human brain. Temporally too, recent advances suggest a convergence between temporal scales addressable with tools like fMRI, which can now investigate delta frequency coherent phenomena, and advanced electromagnetic tools to measure and perturb coherent electrophysiological activity at higher frequencies still. With this convergence in mind, the tools we proposed to develop within the TRDs of the CMM will provide our Collaborative and Service User community with the important ?missing links? between the advances in human cognitive neuroscience at the ?system level,? and the enormous strides in cellular level circuit functional characterization. Our Collaborators will bring their own unique challenges to help us define and further refine these tools, offering problems requiring distinct measures of human brain structural and functional properties in a variety of normal and disease settings. Our Service Users will utilize our tools to better understand human neural systems, and particularly human disease states from multiple sclerosis to Alzheimer?s, to depression and epilepsy. Finally, our Center will seek to disseminate these tools, through open-source software and hardware designs, industrial partnerships and ?hands-on? teaching courses for hardware, and to train a new generation of human neuroscientists in the use of our advanced tools to explore the human brain at this next frontier.